B-cell Acute Lymphoblastic Leukemia Clinical Trial
Official title:
A Early Phase 1 Clinical Trial To Evaluate the Safety and Efficacy of Human CD19 Targeted DASH CAR-T Cells Injection for Subjects With Relapsed/Refractory B-cell Acute Lymphoblastic Leukemia
This study is a single-arm, open-label, dose-escalation trial to explore the safety, tolerability and pharmacokinetic/pharmacodynamics characteristics of human CD19 targeted DASH CAR-T Cells injection, and to preliminarily observe the efficacy of the trial drug in patients with relapsed/refractory B-cell acute lymphoblastic leukemia.
Status | Recruiting |
Enrollment | 9 |
Est. completion date | September 30, 2025 |
Est. primary completion date | September 30, 2024 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years to 70 Years |
Eligibility | Inclusion Criteria:Subjects must meet all of the following criteria to be enrolled: - 18 to 70 years old (including cut-off value), Male and female; - Expected survival > 12 weeks; - ECOG score 0-1; - Bone marrow examination clearly diagnosed as B-cell acute lymphoblastic leukemia, CD19 positive, and who met one of the following conditions: 1. Those who failed to achieve CR after at least 2 courses of standard chemotherapy or had early relapse after complete remission (<12 months) or late relapse after complete remission (= 12 months) and failed to achieve CR after 1 course of standard chemotherapy; 2. For Ph+ ALL: in addition to receiving at least 2 courses of standard chemotherapy, at least two TKIs should be treated with no complete remission or relapse after complete remission; (Patients who cannot tolerate TKI therapy or have TKI treatment contraindications or have T315i mutation are excluded); 3. Those who relapse after stem cell transplantation are not affected by previous treatments; - The venous access required for collection can be established and leukapheresis can be carried according to the judgement of investigators; - Liver, kidney and cardiopulmonary functions meet the following requirements: 1. Serum creatinine = 1.5×ULN; 2. Left ventricular ejection fraction > 50%; 3. Baseline oxygen saturation > 96%; 4. Total bilirubin = 2×ULN; Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) = 3×ULN (As judged by the investigator, the elevation of transaminase caused by the ALL disease itself, ALT and AST = 5×ULN); - Able to understand and sign the Informed Consent Document. Exclusion Criteria:Any one of the following conditions cannot be selected as a subject: - Graft-versus-host disease (GVHD), or need to use immunosuppressants after transplantation; - Patients with hyperleukocytosis (white blood cell count = 50×10^9/L) or whose disease progressed rapidly according to the investigator's judgment at the time of enrollment and cannot ensure the completion of a complete treatment cycle; - Malignant tumors other than acute lymphoblastic leukemia within 5 years prior to screening, in addition to adequately treated cervical carcinoma in situ, basal cell or squamous cell skin cancer, localized prostate cancer after radical resection, ductal carcinoma in situ after radical resection and thyroid cancer after radical resection; - Subjects with positive Hepatitis B surface antigen (HBsAg) or Hepatitis B core antibody (HBcAb) and peripheral blood hepatitis B virus (HBV) DNA titer detection higher than the lower limit of the research center can detect; hepatitis C virus (HCV) antibody positive and peripheral blood HCV RNA positive; human immunodeficiency virus (HIV) antibody positive; syphilis detection positive; - Any instability of systemic disease, including but not limited to unstable angina, cerebrovascular accident, or transient cerebral ischemic (within 6 months prior to screening), myocardial infarction (within 6 months prior to screening), congestive heart failure (New York heart association (NYHA) classification = III), need drug therapy of severe arrhythmia, liver, kidney, or metabolic disease; - Active or uncontrollable infection requiring systemic therapy within 14 days prior to enrollment; - Pregnant or lactating woman, and female subject who plans to have a pregnancy within 1 year after cell transfusion, or male subject whose partner plans to have a pregnancy within 1 year after cell transfusion; - Received CAR-T treatment or other gene therapies before enrollment; - Patients with symptoms of central nervous system; - Subjects who are receiving systemic steroid treatment and requiring long-term systemic steroid treatment during the treatment as determined by the investigator before screening (except inhalation or topical use); - The investigators consider other conditions unsuitable for enrollment. |
Country | Name | City | State |
---|---|---|---|
China | The Second Affiliated Hospital of Nanchang University | Nanchang | Jiangxi |
Lead Sponsor | Collaborator |
---|---|
Hrain Biotechnology Co., Ltd. | Second Affiliated Hospital of Nanchang University |
China,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Dose limited toxicity (DLT) | Safety Indicators | 28 days post infusion | |
Secondary | Pharmacokinetics parameters - the highest concentration of Human CD19 Targeted DASH CAR-T Cells amplified in peripheral blood after reinfusion | Effectiveness Metrics | 2 years post infusion | |
Secondary | Pharmacokinetics parameters - the time to reach the highest concentration of Human CD19 Targeted DASH CAR-T Cells amplified in peripheral blood after reinfusion | Effectiveness Metrics | 2 years post infusion | |
Secondary | Pharmacokinetics parameters - the 28-day area under the curve of Human CD19 Targeted DASH CAR-T Cells amplified in peripheral blood after reinfusion | Effectiveness Metrics | 2 years post infusion | |
Secondary | Pharmacodynamics characteristics - the detection values of IL-6, IFN-?, IL-15 cytokines in peripheral blood | Effectiveness Metrics | 2 years post infusion | |
Secondary | Overall response rate (ORR, include CR and CRi) after administration | Effectiveness Metrics | 3 months post infusion | |
Secondary | Duration of remission (DOR) after administration | Effectiveness Metrics | 2 years post infusion | |
Secondary | Overall Survival (OS) after administration | Effectiveness Metrics | 2 years post infusion |
Status | Clinical Trial | Phase | |
---|---|---|---|
Recruiting |
NCT03671460 -
CD19 CAR-T Cells for Patients With Relapse and Refractory CD19+ B-ALL.
|
Phase 1 | |
Recruiting |
NCT06056752 -
QH103 Cell Injection for the Treatment of Relapsed/Refractory B-cell Acute Lymphoblastic Leukemia
|
Phase 1 | |
Recruiting |
NCT05016947 -
Venetoclax Plus Inotuzumab for B-ALL
|
Phase 1 | |
Suspended |
NCT01974479 -
Pilot Study of Redirected Haploidentical Natural Killer Cell Infusions for B-Lineage Acute Lymphoblastic Leukemia
|
Phase 1 | |
Completed |
NCT00289562 -
Forodesine Hydrochloride (BCX-1777) for B-Cell Acute Lymphoblastic Leukemia
|
Phase 1/Phase 2 | |
Recruiting |
NCT06034275 -
Study of VIP943 in Subjects With Advanced CD123+ Hematologic Malignancies
|
Phase 1 | |
Recruiting |
NCT04191941 -
Treatment of Hematological Malignancy With Novel CAR-T Cells.
|
Early Phase 1 | |
Recruiting |
NCT05333302 -
Pilot CAR-T Cells Therapy for Children/Young Adults With CD19+ R/R Leukemia/Lymphoma
|
Phase 1 | |
Recruiting |
NCT04129099 -
A Study of GC022F CAR-T Cell Immunotherapy for Relapsed or Refractory B- ALL
|
Early Phase 1 | |
Recruiting |
NCT04150497 -
Phase 1/2 Study of UCART22 in Patients With Relapsed or Refractory CD22+ B-cell Acute Lymphoblastic Leukemia (BALLI-01)
|
Phase 1 | |
Withdrawn |
NCT05571540 -
Anti-CD19 Universal CAR-T Cells for r/r CD19+ B-ALL
|
Phase 1/Phase 2 | |
Recruiting |
NCT03281551 -
Efficacy and Safety of PZ01 Treatment in Patients With r/r CD19+ B-cell Acute Lymphoblastic Leukemia/B Cell Lymphoma
|
Phase 1 | |
Recruiting |
NCT05379647 -
Natural Killer (NK) Cell Therapy for B-Cell Malignancies
|
Phase 1 | |
Withdrawn |
NCT04156659 -
Study of Tisagenlecleucel in Chinese Pediatric and Young Adult Subjects With Relapsed or Refractory B-cell ALL
|
Phase 2 | |
Recruiting |
NCT04094311 -
Study of Out of Specification for Tisagenlecleucel
|
Phase 3 | |
Completed |
NCT01207388 -
Confirmatory Phase II Study of Blinatumomab (MT103) in Patients With Minimal Residual Disease of B-precursor Acute Lymphoblastic Leukemia (ALL)
|
Phase 2 | |
Active, not recruiting |
NCT03467256 -
CD19 T-CAR for Treatment of Children and Young Adults With r/r B-ALL
|
Phase 1/Phase 2 | |
Terminated |
NCT04844086 -
RPM CD19-mbIL15-CAR-T Cells in Patient With Advanced Lymphoid Malignancies
|
Phase 1 | |
Recruiting |
NCT05648019 -
CD19-Directed Chimeric Antigen Receptor (CAR) T-Cell Therapy for Relapsed/Refractory B-Lineage Leukaemia / Lymphoma - A Feasibility Protocol
|
Phase 2 | |
Not yet recruiting |
NCT04595162 -
A Study of GC019F CAR-T Cell Immunotherapy for Relapsed or Refractory B- ALL
|
Phase 1 |